This study determined the relationship between mental distress and professional commitment among medical postgraduate students, and the roles of psychological capital as a mediator and the supervisor-postgraduate relationship as a moderator. This cross-sectional study recruited 836 medical postgraduate students from eight medical universities and the medical college of comprehensive universities in Guangdong Province, China. Participants were assessed through questionnaires, which covered demographic items, the supervisor-postgraduate relationship scale, the psychological capital questionnaire, the symptom checklist - 90 (SCL -90), and the professional commitment scale. We used descriptive statistics to describe demographics and mental distress and professional commitment scores. Pearson's analysis was used to identify correlations between the variables and the SPSS PROCESS macro was performed to confirm mediating and moderating effects of psychological capital and the supervisor-postgraduate relationship. Mental distress was negatively related with professional commitment (r = -0.262, p < 0.01) and psychological capital (r = -0.442, p < 0.01). Psychological capital was positively associated with professional commitment (r = 0.486, p < 0.01). The confidence interval (CI) suggested that psychological capital mediated the relationship between mental distress and professional commitment (95% CI, -0.198 to - 0.143), and the supervisor-postgraduate relationship had a moderate role between psychological capital and professional commitment (95% CI, 0.069 to -0.212). Hence, educators may refer to these findings to improve professional commitment level among medical postgraduate students.